Mutations in VCP gene implicated in a number of neurodegenerative diseases

New research, published in Neuron, gives insight into how single mutations in the VCP gene cause a range of neurological conditions including a form of dementia called Inclusion Body Myopathy, Paget's Disease of the Bone and Frontotemporal Dementia (IBMPFD), and the motor neuron disease Amyotrophic Lateral Sclerosis (ALS).

Single mutations in one gene rarely cause such different diseases. This study shows that these mutations disrupt in cells shedding new light on the role of VCP in these multiple disorders.

In healthy cells VCP helps remove damaged mitochondria, the energy-producing engines of cells. The can't do this and as a result, the dysfunctional mitochondria build up.

The new study led by Dr Fernando Bartolome, Dr Helene Plun-Favreau and Dr Andrey Abramov of the UCL Institute of Neurology, found that mitochondria are damaged in cells from patients with mutant VCP. Mitochondria generate a cell's energy, and the study found these damaged mitochondria are less efficient, burning more nutrients but producing less energy. This reduction in available energy makes cells more vulnerable, which could explain why mutations in the VCP gene lead to neurological disorders.

Lead author Dr Fernando Bartolome said "We have found that VCP mutations are associated with mitochondrial dysfunction. VCP had previously been shown to be important in the removal of damaged mitochondria and proteins, accumulation of which is potentially very toxic to cells. A single mutation in the VCP gene could cause multiple because a different type of protein is accumulating in each disorder".

In the study, the researchers used live imaging techniques to examine the functioning of mitochondria in patient cells carrying three independent VCP , and in in which the amount of VCP has been reduced.

"The next step will be to find small molecules able to correct the mitochondrial dysfunction in the VCP deficient cells", added Dr Bartolome .

Dr Brian Dickie, the Association's Director of Research Development says: "Neurons - and motor neurons in particular - are incredibly energy hungry cells. These new findings from the team at UCL show that there is a significant interruption of energy supply in this hereditary form of MND, which has strong implications for understanding the degenerative process underpinning all forms of the disease."

More information: Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels, Neuron.

add to favorites email to friend print save as pdf

Related Stories

An unexpected player in a cancer defense system

Nov 28, 2011

Researchers of the Swedish medical university Karolinska Institutet and the University of Cologne, Germany, have identified a new protein involved in a defense mechanism against cancer. The VCP/p97 complex is best known for ...

Molecular corkscrew

Nov 08, 2011

Scientists from the universities of Zurich and Duisburg-Essen have discovered a specific function of the protein p97/VCP. They demonstrate that the protein repairs DNA breaks like a corkscrew, a repair mechanism that could ...

Recommended for you

Damage to brain networks affects stroke recovery

Nov 21, 2014

(Medical Xpress)—Initial results of an innovative study may significantly change how some patients are evaluated after a stroke, according to researchers at Washington University School of Medicine in St. ...

Dopamine leaves its mark in brain scans

Nov 21, 2014

Researchers use functional magnetic resonance imaging (fMRI) to identify which areas of the brain are active during specific tasks. The method reveals areas of the brain, in which energy use and hence oxygen ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.